This finding might also explain why some prior studies among middle-aged cohorts have failed to find cross-sectional volumetric differences by ɛ4-status.56-58 We found no evidence that the association between APOE-ɛ4 and atrophy in AD-vulnerable regions or regions sensitive to aging (SPARE-BA) was influenced by overall levels of vascular risk, though for the hippocampus, higher vascular risk scores were associated with a stronger relationship between APOE-ɛ4 genetic status and atrophy over time (but this was not significant when excluding ɛ2/ɛ4 carriers). The gene discussed is APOE; the disease is Alzheimer disease.